This R21 application is in response to PA-10-256: Behavioral Regulation Mechanisms of Alcohol Dependence and Related Phenotypes. In persons with alcohol use disorders, conscious attempts to regulate drinking behavior are often undermined by automatic processes that capture attention and instigate arousal in the context of alcohol cues. The persistence of heightened cue reactivity, even following treatment, contributes significantly to the public health burden of the chronic, relapsing disorder of alcohol dependence. Cue reactivity processes involve dynamic feedback loops between the brain and other bodily organs such as the heart. Yet, very little is known about how the brain and heart work together to give rise to heightened alcohol cue reactivity. We propose to address this gap by examining the neurocardiac feedback loop during exposure to alcohol picture cues (Aim 1). Further, there remains a need to develop interventions that effectively diminish reactivity in persons for whom automatic processes, such as those supported by the neurocardiac feedback loop, maintain alcohol cue salience. Thus, we further test whether a brief behavioral manipulation can significantly diminish neural and cardiovascular reactivity to alcohol cues (Aim 2). We will use functional magnetic resonance imaging (fMRI) to capture reactivity of the brain's central autonomic network (CAN) while simultaneously assessing cardiovascular changes during presentation of alcohol-related and neutral picture cues in a group of 24 non-treatment seeking emerging adults with alcohol dependence (DEP) compared to a matched sample of moderate drinking controls (MOD). Activation in selected CAN structures (medial prefrontal cortex, insula, brain stem) and neurocardiac signal variability (heart rate variability and blood pressure variability) in response to alcohol cues will be simultaneously assessed. Specific Aim 1 will examine differences in alcohol cue reactivity between DEP and MOD young adults in terms of brain activation, effective connectivity, and physiological measures of neurocardiac signaling. Specific Aim 2 will explore whether a behavioral manipulation of breathing at 0.1 Hz reduces neural and/or cardiovascular reactivity to alcohol cues. If successful, this application will yield support for a new approach wherein neurocardiac signaling can be linked in a time-varying manner to neural systems that modulate cue reactivity. Its potential public health significance is in exploring a behavioral regulation intervention that would be amenable to large scale dissemination and could be used within the treatment context or ad lib during moments of heightened vulnerability to relapse.